title: Use of linkage analysis, genome-wide association studies, and next-generation sequencing in the identification of disease-causing mutations.
abstract: For the past two decades, linkage analysis and genome-wide analysis have greatly advanced our knowledge of the human genome. But despite these successes the genetic architecture of diseases remains unknown. More recently, the availability of next-generation sequencing has dramatically increased our capability for determining DNA sequences that range from large portions of one individual's genome to targeted regions of many genomes in a cohort of interest. In this review, we highlight the successes and shortcomings that have been achieved using genome-wide association studies (GWAS) to identify the variants contributing to disease. We further review the methods and use of new technologies, based on next-generation sequencing, that are becoming increasingly used to expand our knowledge of the causes of genetic disease.
authors.affiliation: Computational Medicine Center, Thomas Jefferson University Jefferson Medical College, Philadelphia, PA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Londin
authors.forename: Priyanka
authors.initials: P
authors.lastname: Yadav
authors.forename: Saul
authors.initials: S
authors.lastname: Surrey
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Kricka
authors.forename: Paolo
authors.initials: P
authors.lastname: Fortina
mesh_terms: D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D009154:Mutation / Q000235:genetics